scholarly journals Effects of low-to-moderate ethanol consumption on colonic growth and gene expression in young adult and middle-aged male rats

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243499
Author(s):  
Nicole Wells ◽  
Jacqueline Quigley ◽  
Jeremy Pascua ◽  
Natalie Pinkowski ◽  
Lama Almaiman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Differentiation ◽  
Young Adult ◽  
Cell Growth ◽  
Alcohol Consumption ◽  
Ethanol Consumption ◽  
Ethanol Treatment ◽  
Middle Aged

Excessive alcohol consumption is a risk factor associated with colorectal cancer; however, some epidemiological studies have reported that moderate alcohol consumption may not contribute additional risk or may provide a protective effect reducing colorectal cancer risk. Prior research highlights the importance of proliferation, differentiation, and apoptosis as parameters to consider when evaluating colonic cell growth and tumorigenesis. The present study investigated whether chronic low-to-moderate ethanol consumption altered these parameters of colonic cell growth and expression of related genes. Twenty-four nondeprived young adult (109 days old) and 24 nondeprived middle-aged (420 days old) Wistar rats were randomly assigned to an ethanol-exposed or a water control group (n = 12/group). The ethanol group was provided voluntary access to a 20% v/v ethanol solution on alternate days for 13 weeks. Colon tissues were collected for quantitative immunohistochemical analyses of cell proliferation, differentiation and apoptosis using Ki-67, goblet cell and TUNEL, respectively. Gene expression of cyclin D1 (Ccnd1), Cdk2, Cdk4, p21waf1/cip1 (Cdkn1a), E-cadherin (Cdh1) and p53 were determined by quantitative real-time polymerase chain reaction in colonic scraped mucosa. Ethanol treatment resulted in a lower cell proliferation index and proliferative zone, and lower Cdk2 expression in both age groups, as well as trends toward lower Ccnd1 and higher Cdkn1a expression. Cell differentiation was modestly but significantly reduced by ethanol treatment only in older animals. Overall, older rats showed decreases in apoptosis and gene expression of Cdk4, Cdh1, and p53 compared to younger rats, but there was no observed effect of ethanol exposure on these measures. These findings suggest that low-to-moderate ethanol consumption improves at least one notable parameter in colonic tumorigenesis (cell proliferation) and associated gene expression regardless of age, however, selectively decreased cell differentiation among older subjects.

Effects of Low‐to‐Moderate Ethanol Consumption on Colonic Cell Proliferation, Differentiation and Apoptosis in Young Adult and Middle‐Aged Rats

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Luciano Voutour ◽  
Yuko Murase ◽  
Nicole Wells ◽  
Jacqueline Quigley ◽  
Jeremy Pascua ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Young Adult ◽  
Ethanol Consumption ◽  
Aged Rats ◽  
Middle Aged

The ERK pathway involves positive and negative regulations of HT-29 colorectal cancer cell growth by extracellular zinc

2003 ◽  
Vol 285 (6) ◽  
pp. G1181-G1188 ◽  
Author(s):  
Ki-Sook Park ◽  
Nam-Gu Lee ◽  
Ki-Hoo Lee ◽  
Jeong Taeg Seo ◽  
Kang-Yell Choi
Keyword(s):  
Colorectal Cancer ◽  
Signal Transduction ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cyclin D1 ◽  
Growth Regulation ◽  
Erk Pathway ◽  
Differential Growth ◽  
Erk Activation ◽  
Ht 29

Dietary zinc is an important trace element in the body and is related to both cell proliferation and growth arrest. A recent study found that extracellular zinc-sensing receptors trigger intracellular signal transduction in HT-29 human colorectal cancer cells. However, the signaling mechanism causing this growth regulation by extracellular zinc is not clearly understood. At 10- and 100-μM levels of ZnCl2 treatment, HT-29 cell growth and proliferation increased and decreased, respectively, in a minimally serum-starved medium (MSSM). A lack of significant increase in intracellular zinc levels after zinc treatment suggested that this differential growth regulation of HT-29 cells by extracellular zinc is acquired by receptor-mediated signal transduction. Moreover, this zinc-induced growth regulation was differentially affected by PD-98059, suggesting the involvement of the ERK pathway. Transient ERK activation and subsequent cyclin D1 induction were observed on adding 10 μM ZnCl2 in MSSM in the presence of cell proliferation. On the other hand, prolonged ERK activity was observed with a subsequent increase of cyclin D1 and p21Cip/WAF1 on adding 100 μM ZnCl2 in MSSM, and this was associated with nonproliferation. Moreover, this ERK activation and cyclin D1 and p21Cip/WAF1 induction were abolished by PD-98059 pretreatment. The differential regulations of cell growth, ERK activities, and cyclin D1 and p21Cip/WAF1 inductions were also observed in serum-enriched medium containing higher zinc concentrations. Therefore, differential cell cycle regulator induction occurs by a common ERK pathway in the differential growth regulation of HT-29 cells by extracellular zinc.

scholarly journals EFFECTS OF MODERATE ETHANOL CONSUMPTION ON EXPRESSION OF GENES RELATED TO COLONIC CELL GROWTH IN YOUNG ADULT AND OLDER RATS

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
Nicole Wells ◽  
Jacqueline Quigley ◽  
Jeremy Pascua ◽  
Natalie Pinkowski ◽  
Lama Almaiman ◽  
...  
Keyword(s):  
Young Adult ◽  
Cell Growth ◽  
Ethanol Consumption ◽  
Expression Of Genes

scholarly journals Interleukin-34 Enhances the Tumor Promoting Function of Colorectal Cancer-Associated Fibroblasts

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3537
Author(s):  
Eleonora Franzè ◽  
Antonio Di Grazia ◽  
Giuseppe Sigismondo Sica ◽  
Livia Biancone ◽  
Federica Laudisi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Associated Fibroblasts ◽  
Cancer Cell Proliferation ◽  
Fibroblast Growth ◽  
Stromal Compartment ◽  
Large Numbers ◽  
And Migration ◽  
Proliferation And Migration

The stromal compartment of colorectal cancer (CRC) is marked by the presence of large numbers of fibroblasts, termed cancer-associated fibroblasts (CAFs), which promote CRC growth and progression through the synthesis of various molecules targeting the neoplastic cells. Interleukin (IL)-34, a cytokine over-produced by CRC cells, stimulates CRC cell growth. Since IL-34 also regulates the function of inflammatory fibroblasts, we hypothesized that it could regulate the tumor promoting function of colorectal CAFs. By immunostaining and real-time PCR, we initially showed that IL-34 was highly produced by CAFs and to lesser extent by normal fibroblasts isolated from non-tumoral colonic mucosa of CRC patients. CAFs and normal fibroblasts expressed the functional receptors of IL-34. IL-34 induced normal fibroblasts to express α-SMA, vimentin and fibroblast activation protein and enhanced fibroblast growth, thus generating a cellular phenotype resembling that of CAFs. Consistently, knockdown of IL-34 in CAFs with an antisense oligonucleotide (AS) decreased expression of such markers and inhibited cell proliferation. Co-culture of CRC cells with IL-34 AS-treated CAFs supernatants resulted in less cancer cell proliferation and migration. Among CAF-derived molecules known to promote CRC cell growth/migration, only netrin-1 and basic-fibroblast growth factor were induced by IL-34. Data suggest a role for IL-34 in the control of colorectal CAF function.

scholarly journals Microarray and Suppression Subtractive Hybridization Analyses of Gene Expression in Pheochromocytoma Cells Reveal Pleiotropic Effects of Pituitary Adenylate Cyclase-Activating Polypeptide on Cell Proliferation, Survival, and Adhesion

Endocrinology ◽  
2003 ◽  
Vol 144 (6) ◽  
pp. 2368-2379 ◽  
Author(s):  
Luca Grumolato ◽  
Abdel G. Elkahloun ◽  
Hafida Ghzili ◽  
David Alexandre ◽  
Cédric Coulouarn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Cell Differentiation ◽  
Adenylate Cyclase ◽  
Pc12 Cells ◽  
Suppression Subtractive Hybridization ◽  
Global Gene Expression ◽  
Subtractive Hybridization ◽  
Neuroendocrine Cells ◽  
Pituitary Adenylate Cyclase

Abstract Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts trophic effects on several neuronal, neuroendocrine, and endocrine cells. To gain insight into the pattern of the transcriptional modifications induced by PACAP during cell differentiation, we studied the effects of this neuropeptide on rat pheochromocytoma PC12 cells. We first analyzed the transcriptome of PC12 cells in comparison to that of terminally differentiated rat adrenomedullary chromaffin cells, using a high-density microarray, to identify genes associated with the proliferative phenotype that are possible targets of PACAP during differentiation of sympathoadrenal normal and tumoral cells. We then studied global gene expression in PC12 cells after 48 h of exposure to PACAP, using both cDNA microarray and suppression subtractive hybridization technologies. These complementary approaches resulted in the identification of 75 up-regulated and 70 down-regulated genes in PACAP-treated PC12 cells. Among the genes whose expression is modified in differentiated cells, a vast majority are involved in cell proliferation, survival, and adhesion/motility. Expression changes of most of these genes have been associated with progression of several neoplasms. A kinetic study of the effects of PACAP on some of the identified genes showed that the neuropeptide likely exerts early as well as late actions to achieve the gene expression program necessary for cell differentiation. In conclusion, the results of the present study underscore the pleiotropic role of PACAP in cell differentiation and provide important information on novel targets that could mediate the effects of this neuropeptide in normal and tumoral neuroendocrine cells.

Novel mechanism linking noncanonical Wnt ligand induction to suppression of colorectal cancer cell proliferation.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 648-648
Author(s):  
Donald Peter Braun ◽  
Bani M Fagla ◽  
Irshad Ali
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Wnt Pathway ◽  
Fold Increase ◽  
Canonical Pathway ◽  
Unexpected Finding ◽  
Cancer Cell Proliferation ◽  
Pathway Gene ◽  
Proliferation And Differentiation

648 Background: Malignant tissues are characterized by uncontrolled proliferation and dysfunctional differentiation. A central pathway in the control of proliferation and differentiation is the Wnt pathway. Wnt function is mediated by a canonical pathway (CP) which utilizes β-catenin and stimulates cell proliferation, and a non-canonical pathway (NCP) independent of β-catenin involved with differentiation. Studies suggest that dysfunctional Wnt signaling results from imbalance of CP components. The possibility that modulation of NCP components are involved in this process has not been studied comprehensively. Given their importance in constraining CP signaling and proliferation, the purpose of this study was to determine the capacity of NCP components to suppress human colorectal cancer (CRC) proliferation. Methods: Short term, primary CRC lines were established from resected tumors from patients with metastatic and/or recurrent disease. CRC were treated with LiCl, an activator of the CP, Dkk1, an inhibitor of the CP, and IWP-2, a pan inhibitor of CP and NCP Wnt ligand secretion. CRC proliferation and Wnt pathway gene expression were determined by MTS assays and quantitative gene expression respectively. Results: Unexpectedly, CRC proliferation was inhibited significantly (p<0.01) by LiCl and stimulated modestly (ns) by Dkk1. This was associated with a 20 fold increase in gene expression for the NCP ligand, Wnt9A. LiCl treated cells incubated with IWP-2 reversed the unexpected LiCl-mediated suppression of CRC proliferation. Conclusions: The unexpected finding that LiCl suppresses proliferation and Dkk1 has the opposite effect indicate dysregulation of the Wnt pathway in CRC. Further support for this hypothesis is the fact that Wnt 9A, an NCP ligand is increased by LiCl in CRC, an effect that is not expected in non-malignant cells. That IWP-2, a pan Wnt ligand secretion inhibitor reverses these effects is consistent with these observations. This study is the first to demonstrate a correlation between NCP ligand induction and suppression of CRC proliferation and suggests that control of CRC proliferation may be achieved in patients by modalities that activate the NCP Wnt pathway.

scholarly journals Polysome arrest restricts miRNA turnover by preventing exosomal export of miRNA in growth-retarded mammalian cells

2015 ◽  
Vol 26 (6) ◽  
pp. 1072-1083 ◽  
Author(s):  
Souvik Ghosh ◽  
Mainak Bose ◽  
Anirban Ray ◽  
Suvendra N. Bhattacharyya
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Subcellular Distribution ◽  
Mammalian Cells ◽  
Cellular Response ◽  
Mature Mirnas ◽  
Regulatory Rnas ◽  
The Stability ◽  
External Stimuli

MicroRNAs (miRNAs) are tiny posttranscriptional regulators of gene expression in metazoan cells, where activity and abundance of miRNAs are tightly controlled. Regulated turnover of these regulatory RNAs is important to optimize cellular response to external stimuli. We report that the stability of mature miRNAs increases inversely with cell proliferation, and the increased number of microribonucleoproteins (miRNPs) in growth-restricted mammalian cells are in turn associated with polysomes. This heightened association of miRNA with polysomes also elicits reduced degradation of target mRNAs and impaired extracellular export of miRNA via exosomes. Overall polysome sequestration contributes to an increase of cellular miRNA levels but without an increase in miRNA activity. Therefore miRNA activity and turnover can be controlled by subcellular distribution of miRNPs that may get differentially regulated as a function of cell growth in mammalian cells.

scholarly journals Coiled-Coil Domain Containing 80 Suppresses Nonylphenol-Induced Colorectal Cancer Cell Proliferation by Inhibiting the Activation of ERK1/2

2021 ◽  
Vol 9 ◽  
Author(s):  
Jing Wang ◽  
Yuan-wei Zhang ◽  
Nian-jie Zhang ◽  
Shuo Yin ◽  
Du-ji Ruan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Differentially Expressed Genes ◽  
Endocrine Disrupting Chemicals ◽  
Coiled Coil ◽  
Underlying Mechanism ◽  
Differentially Expressed ◽  
Coiled Coil Domain ◽  
Upregulated Genes

Recently, the effect of endocrine-disrupting chemicals on the cancer procession has been a concern. Nonylphenol (NP) is a common environmental estrogen that has been shown to enhance the proliferation of colorectal cancer (CRC) cells in our previous studies; however, the underlying mechanism remains unclear. In this study, we confirmed the increased concentration of NP in the serum of patients with CRC. RNA sequencing was used to explore the differentially expressed genes after NP exposure. We found 16 upregulated genes and 12 downregulated genes in COLO205 cells after NP treatment. Among these differentially expressed genes, we found that coiled-coil domain containing 80 (CCDC80) was downregulated by NP treatment and was associated with CRC progression. Further experiments revealed that the overexpression of CCDC80 significantly suppressed NP-induced cell proliferation and recovered the reduced cell apoptosis. Meanwhile, the overexpression of CCDC80 significantly inhibited the activation of ERK1/2 induced by NP treatment. ERK1/2 inhibitor (PD98059) treatment also suppressed NP-induced CRC cell growth, but the overexpression of CCDC80 did not enhance the effect of ERK1/2 inhibitor. Taken together, NP treatment significantly inhibited the expression of CCDC80, and the overexpression of CCDC80 suppressed NP-induced CRC cell growth by inhibiting the activation of ERK1/2. These results suggest that NP could induce CRC cell growth by influencing the expression of multiple genes. CCDC80 and ERK1/2 inhibitors may be suitable therapeutic targets in NP-related CRC progression.

scholarly journals An IRF4-MYC-mTORC1 integrated pathway controls cell growth and the proliferative capacity of activated B cells during B cell differentiation in vivo

2021 ◽  
Author(s):  
Dillon G Patterson ◽  
Anna K Kania ◽  
Madeline J Price ◽  
James R Rose ◽  
Christopher D Scharer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Differentiation ◽  
B Cells ◽  
Cell Growth ◽  
B Cell ◽  
Proliferative Response ◽  
Cell Activation ◽  
B Cell Differentiation ◽  
B Cell Activation

Cell division is an essential component of B cell differentiation to antibody-secreting plasma cells, with critical reprogramming occurring during the initial stages of B cell activation. However, a complete understanding of the factors that coordinate early reprogramming events in vivo remain to be determined. In this study, we examined the initial reprogramming by IRF4 in activated B cells using an adoptive transfer system and mice with a B cell-specific deletion of IRF4. IRF4-deficient B cells responding to influenza, NP-Ficoll and LPS divided, but stalled during the proliferative response. Gene expression profiling of IRF4-deficient B cells at discrete divisions revealed IRF4 was critical for inducing MYC target genes, oxidative phosphorylation, and glycolysis. Moreover, IRF4-deficient B cells maintained an inflammatory gene expression signature. Complementary chromatin accessibility analyses established a hierarchy of IRF4 activity and identified networks of dysregulated transcription factor families in IRF4-deficient B cells, including E-box binding bHLH family members. Indeed, B cells lacking IRF4 failed to fully induce Myc after stimulation and displayed aberrant cell cycle distribution. Furthermore, IRF4-deficient B cells showed reduced mTORC1 activity and failed to initiate the B cell-activation unfolded protein response and grow in cell size. Myc overexpression in IRF4-deficient was sufficient to overcome the cell growth defect. Together, these data reveal an IRF4-MYC-mTORC1 relationship critical for controlling cell growth and the proliferative response during B cell differentiation.

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